Concomitant Administration of VEGFR Tyrosine Kinase and Proton Pump Inhibitors May Impair Clinical Outcome of Patients With Metastatic Renal Cancer.

• The extensive use of PPIs can interfere with the efficacy of oral therapies. • PPIs affect the survival of mRCC patients treated with pazopanib and cabozantinib. • The concomitant use of PPIs and TKIs requires an evaluation of benefits and risks. The administration of proton pump inhibitors (PPIs) is a common practice to reduce gastro-esophageal adverse events associated with drug treatments but may impair absorption and exposure to oncology drugs. This study investigated the effect of concomitant administration of PPIs and pazopanib, sunitinib and cabozantinib on survival of patients with metastatic clear cell renal carcinoma (mRCC). Total 451 patients receiving pazopanib, sunitinib and cabozantinib as first line treatment were enrolled in this retrospective study. Patients were defined as "no concomitant PPIs (PPI−)" if no PPIs were administered during TKIs, and as "concomitant PPIs (PPI+)" if the administration of PPIs was at least 75% of the time during which TKIs were given. Eighty patients administered pazopanib were PPI− and 86 PPI+; no difference in PFS was observed (10.7 vs. 11.9 months, P =.79). If patients were stratified as short (n = 89) and long (n = 77) responders, there was a significant difference in terms of PFS in PPI+ (n = 47) versus PPI− (n = 30) in long responders, being 24.7 versus 38 months (P =.04), respectively. In the sunitinib cohort, no significant difference of PFS in PPI+ (n = 102) versus PPI− (n = 131) was found, being 11.3 versus 18.1 months, respectively (P =0.15). In the cabozantinib cohort, there was a statistically significant difference in PFS of PPI+ versus PPI− (6 months vs. not reached, P =.04). No correlation with adverse events was found. This study demonstrates an association between PPIs and impaired PFS in mRCC patients given pazopanib and cabozantinib and recommends caution on their concomitant use. The extensive use of proton pump inhibitors (PPIs) poses the problem of their interference on the absorption of oral therapies and on the efficacy of the therapy. This study demonstrates an association between administration of PPIs and impaired PFS in mRCC patients treated with pazopanib and cabozantinib. It is recommended caution when prescribing PPIs and TKIs. [ABSTRACT FROM AUTHOR]